Smoking is the leading cause of preventable health-related morbidity and mortality in the United States. However, millions of individuals decide to begin to smoke or continue to smoke despite this widespread knowledge, suggesting that risk taking behavior may differ between smokers and nonsmokers. Furthermore, although the major reason people attempt to quit smoking is to improve their health and longevity the overwhelming majority of quit attempts fail, suggesting that smoking cessation may also alter risk taking behavior. The proposed research will combine ASL perfusion and BOLD functional MRI with well- validated behavior paradigms to functionally characterize the dopaminergic mesolimbic- frontal system, which subserves decisions under risk, in N=24 control subjects and N=24 active smokers before and after smoking abstinence, in order to test the hypothesis that smoking is associated with differential function of this mesolimbic system, and that smoking abstinence alters mesolimbic tone. Because the tone in the mesolimbic system can be pharmacologically, physiologically, and potentially behaviorally modulated, the identification of alterations in the functioning of this system in active and/or abstinent smokers may suggest novel strategies to reduce smoking drive and increase quit success. PUBLIC HEALTH RELEVANCE: This project will combine brain imaging methods with well-validated behavior paradigms to measure brain activity of chronic smokers during performing the balloon analog risk task (BART) and at rest while smoking as usual and after 48 hours of smoking abstinence, which will be compared to brain activity of matched healthy controls, in order to functionally characterize the dopaminergic mesolimbic-frontal system in chronic smokers and test the hypothesis that smoking is associated with differential function of this mesolimbic-frontal system, and that smoking abstinence alters mesolimbic tone. Because the tone in the mesolimbic system can be pharmacologically, physiologically, and potentially behaviorally modulated, the identification of alterations in the functioning of this system in actie and/or abstinent smokers may suggest novel strategies to reduce smoking drive and increase quit success.